Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies.However,the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression.Here,we propose a self-amplifying logic-gated gene editing strategy for gene/H_(2)O_(2)-mediated/starvation multimodal cancer therapy.In this approach,a hypoxia-degradable covalent-organic framework(COF) is synthesized to coat a-ZIF-8 in which glucose oxidase(GOx) and CRISPR system are packaged.To intensify intracellular redox dyshomeostasis,DNAzymes which can cleave catalase mRNA are loaded as well.When the nano system gets into the tumor,the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx,which amplifies intracellular H^(+)and hypoxia,accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells.These tandem reactions deplete glucose and oxygen,leading to logic-gated-triggered gene editing as well as synergistic gene/H_(2)O_(2)-mediated/starvation therapy.Overall,this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Organic-inorganic bismuth （lll）-based material： A lead- free, air-stable and solution-processable light-absorber beyond organolead perovskites

Methylammonium bismuth （III） iodide single crystals and films have been developed and investigated. We have further presented the first demonstration of using this organic-inorganic bismuth-based material to replace lead/tin-based perovskite materials in solution-processable solar cells. The organic-inorganic bismuth-based material has advantages of non-toxicity, ambient stability, and low-temperature solution-processability, which provides a promising solution to address the toxicity and stability challenges in organolead- and organotin-based perovskite solar cells. We also demonstrated that trivalent metal cation-based organic-inorganic hybrid materials can exhibit photovoltaic effect, which may inspire more research work on developing and applying organic-inorganic hybrid materials beyond divalent metal cations （Pb （II） and Sn （II）） for solar energy applications.